Barmin Roman A, Maksimova Elizaveta A, Rudakovskaya Polina G, Gayer Alexey V, Shirshin Evgeny A, Petrov Kirill S, Terentyeva Daria A, Gusliakova Olga I, Sindeeva Olga A, Klimenko Oleg A, Chuprov-Netochin Roman N, Solovev Alexander A, Huang Gaoshan, Ryabova Anastasia V, Loschenov Victor B, Gorin Dmitry A
Skolkovo Institute of Science and Technology, 3 Nobelya Str., Moscow 121205, Russia.
Skolkovo Institute of Science and Technology, 3 Nobelya Str., Moscow 121205, Russia.
Colloids Surf B Biointerfaces. 2022 Nov;219:112856. doi: 10.1016/j.colsurfb.2022.112856. Epub 2022 Sep 17.
Gas-liquid interfaces are reaching a particular interest in biomedicine. Microbubbles, ultrasound contrast agents of clinical routine, gained increasing attention as theranostic platforms due to the preserved acoustic response, drug conjugation capabilities, and applicability in biological barrier opening. A combination of microbubbles and photodynamic therapy agents can enhance the photodynamic effect, yet the evaluation of agent conjugation on microbubble stabilization and photodynamic effect is needed. Hence, two commercially available phthalocyanine photosensitizers - Holosens® (ZnPc) and Photosens® (AlPc) - were coupled with bovine serum albumin before microbubble synthesis. We demonstrated an albumin: phthalocyanine ratio of 1:1 and covalent attachment for ZnPc, a ratio of 1:3 with electrostatic binding for AlPc. Submicron-sized microbubbles (air- and SF- filled) had a diameter of 0.8 µm. Albumin-phthalocyanine conjugates increased the microbubble concentration and shelf-life stability compared to plain ones. We hypothesized that phthalocyanine fluorescence lifetime values decreased after conjugation with microbubbles due to narrow distance between conjugates in the shell. Agents based on AlPc demonstrated higher photodynamic activity than agents based on ZnPc, and microbubbles preserved acoustic stability in human blood plasma. The biodistribution of AlPc-conjugated microbubbles was evaluated. We conclude that our microbubble platforms demonstrate greater photodynamic activity and prolonged stability for further applications in photodynamic therapy.
气液界面在生物医学领域正引起特别的关注。微泡作为临床常规超声造影剂，由于其保留的声学响应、药物偶联能力以及在生物屏障开放方面的适用性，作为诊疗一体化平台受到越来越多的关注。微泡与光动力治疗剂的组合可以增强光动力效应，但需要评估试剂偶联对微泡稳定性和光动力效应的影响。因此，在微泡合成之前，将两种市售的酞菁光敏剂——Holosens®（锌酞菁）和Photosens®（铝酞菁）与牛血清白蛋白偶联。我们证明了锌酞菁的白蛋白与酞菁比例为1:1且为共价连接，铝酞菁的比例为1:3且为静电结合。亚微米级微泡（空气填充和六氟化硫填充）的直径为0.8微米。与普通微泡相比，白蛋白 - 酞菁偶联物提高了微泡浓度和保质期稳定性。我们推测，由于壳层中偶联物之间距离较窄，酞菁与微泡偶联后荧光寿命值会降低。基于铝酞菁的试剂比基于锌酞菁的试剂表现出更高的光动力活性，并且微泡在人血浆中保持声学稳定性。评估了铝酞菁偶联微泡的生物分布。我们得出结论，我们的微泡平台表现出更大的光动力活性和更长的稳定性，可用于光动力治疗的进一步应用。
